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N,O‐Acetals from Pivalaldehyde and Amino Acids for the α‐Alkylation with Self‐Reproduction of the Center of Chirality. Enolates of 3‐Benzoyl‐2‐( tert ‐butyl)‐1,3‐oxazolidin‐5‐ones
Author(s) -
Seebach Dieter,
Fadel Antoine
Publication year - 1985
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19850680521
Subject(s) - chemistry , tetrahydrofuran , alkylation , racemization , benzaldehyde , benzyl bromide , medicinal chemistry , lithium (medication) , deprotonation , hydrolysis , benzoyl chloride , chirality (physics) , bromide , stereochemistry , organic chemistry , solvent , catalysis , chiral symmetry breaking , physics , quantum mechanics , quark , endocrinology , medicine , ion , nambu–jona lasinio model
The sodium salts of ( S )‐alanine, ( S )‐phenylalanine, ( S )‐valine, and ( S )‐methionine are condensed with pivalaldehyde to imines 5 . Cyclization by treatment with benzoyl chloride in cold CH 2 Cl 2 gives mainly (4:1 to > 99:1) the (2 S ,4 S )‐4‐alkyl‐3‐benzoyl‐2‐( tert ‐butyl)‐1,3‐oxazolidin‐5‐ones ( 6 ; cis ‐configuration) in high yields (85–95%). The oxazolidinones 6 and 7 are deprotonated with lithium diethylamide (LDEA) in tetrahydrofuran (THF) and alkylated (Mel, benzyl bromide) or hydroxyalkylated (benzaldehyde) to 4,4‐disubstituted oxazolidinones 9 and 10 , respectively, with high diastereoselectivity (9:1 to 50:1; relative topicity ul ). Hydrolysis of three of the oxazolidinones to amino acids of known configuration and optical purity indicates that little if any racemization occurs in the process.